Depressed contractility has been demonstrated in cardiac failure. Though separate studies have been done in elucidating the defects, no clear picture has evolved in deciding whether the fault is in the excitation-contraction coupling or the myofibrils or both. Thus we propose to examine systematically all the systems, namely sarcolemma, sarcoplasmic reticulum and myofibrils, that would contribute to depression in contractility at the same stage of cardiac failure. We will trace the time course of changes in these systems during the life span (prenecrotic, necrotic, hypertrophic and failure stages) of the Syrian hamsters with an hereditary cardiomyopathy, which provides a reproducible model of spontaneous heart failure. The criteria for monitoring changes in these systems will be the measurement of (Na ions plus K ions) ATPase, adenyl cyclase, calcium binding (for purified sarcolemma), formation and decomposition of phosphorylated intermediate of Ca ions ATPase, (for sarcoplasmic reticulum) and EGTA-sensitive Mg ions ATPase (for purified myofibrils). Structural changes in the sarcolemma and sarcoplasmic reticulum will be followed by electron spin resonance spectroscopy. The goal is to elucidate the mechanism underlying the dysfunction in cardiac failure in the hamsters and ultimately devise countermeasures to combat cardiomyopathy.